1
00:00:04,460 --> 00:00:07,170 Hello and welcome
to Mayo Clinic Talks, 2
00:00:07,170 --> 00:00:09,030 The Opioid Edition.
3
00:00:09,030 --> 00:00:11,370 I'm Tracy McCray and
is was the second of 4
00:00:11,370 --> 00:00:14,145 two bonus episodes on
the opioid crisis. 5
00:00:14,145 --> 00:00:15,750 This podcast is brought to 6
00:00:15,750 --> 00:00:17,520 you by the opioid
conference, 7
00:00:17,520 --> 00:00:19,050 held each year as part of 8
00:00:19,050 --> 00:00:21,675 Mayo Clinic’s continuing medical education.
9
00:00:21,675 --> 00:00:23,010 For more information on
10
00:00:23,010 --> 00:00:24,840 all opioid episodes
11
00:00:24,840 --> 00:00:28,395 available for credit, visit 12
00:00:28,395 --> 00:00:30,840 ce.mayo.edu/opioidpc.
00:00:30,840 --> 00:00:32,730 Today we are showcasing Dr. Molly 14 00:00:32,730 --> 00:00:34,710 Feely, a consultant in the division of 15 00:00:34,710 --> 00:00:36,150 General Internal Medicine 16
00:00:36,150 --> 00:00:37,815 at Mayo Clinic, Rochester. 17
00:00:37,815 --> 00:00:39,930 She will be sharing
best practices for 18 00:00:39,930 --> 00:00:42,684 management of opioid side effects. 19 00:00:42,684 --> 00:00:44,810 I'm going to spend
a little time talking 20
00:00:44,810 --> 00:00:47,090 about opioid side effects. 21
00:00:47,090 --> 00:00:48,200 And I have no financial
22
00:00:48,200 --> 00:00:49,610 relationships with anybody. 23 00:00:49,610 --> 00:00:51,845 I am going to talk about a number of 24 00:00:51,845 --> 00:00:53,929 off-label uses of medications
25
00:00:53,929 --> 00:00:55,790 and I'll talk about
that as I go along. 26 00:00:55,790 --> 00:00:57,920 There's a lot of side effects 27 00:00:57,920 --> 00:01:00,500 related to opioid pain medications. 28 00:01:00,500 --> 00:01:02,870 And pointing out
the fact that 29
00:01:02,870 --> 00:01:03,890 we're really only
going to talk 30
00:01:03,890 --> 00:01:05,345 about four of them today. 31
00:01:05,345 --> 00:01:07,400 And what we're going
to try to talk about; 32 00:01:07,400 --> 00:01:09,470 our objectives are recognizing 33 00:01:09,470 --> 00:01:11,510 which opiate side
effects are typically 34
00:01:11,510 --> 00:01:14,480 transient and which
are more pervasive. 35
00:01:14,480 --> 00:01:16,700 To talk about
36
00:01:16,700 --> 00:01:19,385 each opioid side
effect discussed 37 00:01:19,385 --> 00:01:21,830 and distinguish when to rotate to 38 00:01:21,830 --> 00:01:23,540 a different opioid versus when 39 00:01:23,540 --> 00:01:25,595 to just treat
through the symptom. 40
00:01:25,595 --> 00:01:27,290 And the way we're
gonna do this is we're 41
00:01:27,290 --> 00:01:29,495 going to have a case
42
00:01:29,495 --> 00:01:30,560 and then we're going to
43
00:01:30,560 --> 00:01:31,790 talk about the principles 44 00:01:31,790 --> 00:01:34,370 related to that opioid side-effect, 45 00:01:34,370 --> 00:01:36,050 talk about some
tips and manage 46
00:01:36,050 --> 00:01:37,850 mean that opioid
side effect, 47
and then we'll have some take-home points 48
00:01:40,265 --> 00:01:41,510 and we'll do that for each 49
00:01:41,510 --> 00:01:42,950 side effect we talk about. 50
00:01:42,950 --> 00:01:45,125 We're talking about
constipation first, 51
00:01:45,125 --> 00:01:47,390 and this is an actual
patient I took care of. 52
00:01:47,390 --> 00:01:49,550 It's probably been
about two years now, 53
00:01:49,550 --> 00:01:51,710 but she was 37-years-old. 54
00:01:51,710 --> 00:01:53,750 She had widely metastatic 55
00:01:53,750 --> 00:01:56,465 breast cancer to the bones 56
00:01:56,465 --> 00:01:58,850 and she when she
presented to my office, 57
00:01:58,850 --> 00:02:01,565 she had had no bowel
movement in the last 8 58
00:02:01,565 --> 00:02:04,955 days and she was miserable. 59
She was so miserable 60
00:02:06,560 --> 00:02:08,060 that she actually
quit taking 61
00:02:08,060 --> 00:02:10,385 all of her opioid
pain medications 62
00:02:10,385 --> 00:02:13,160 a couple days prior to
coming to my office, 63
00:02:13,160 --> 00:02:14,675 and that's significant.
64
00:02:14,675 --> 00:02:17,975 She took off her 75
microgram fentanyl patch 65
00:02:17,975 --> 00:02:19,220 and she stopped all of
66
00:02:19,220 --> 00:02:21,065 her oral hydromorphone.
67
00:02:21,065 --> 00:02:23,480 She did have a bowel
regimen at home. 68
00:02:23,480 --> 00:02:25,070 She had docusate, a
69
00:02:25,070 --> 00:02:27,845 100-milligrams, as-
needed twice a day. 70
00:02:27,845 --> 00:02:29,810 She had milk of magnesia 30cc’s 71
three times a day, as needed 72
00:02:32,825 --> 00:02:35,300 and Miralax 17 grams
73
00:02:35,300 --> 00:02:37,805 in water, daily as needed. 74 00:02:37,805 --> 00:02:39,695 So my question is, 75 00:02:39,695 --> 00:02:42,290 in addition to a successful enema 76 00:02:42,290 --> 00:02:43,670 in the office, 77 00:02:43,670 --> 00:02:45,260 which of the following would be 78 00:02:45,260 --> 00:02:46,835 the next best step
79 00:02:46,835 --> 00:02:48,695 in managing her constipation? 80 00:02:48,695 --> 00:02:53,600 Adding sorbitol 30cc’s BO PO BID PRN, 81 00:02:53,600 --> 00:02:56,150 adding a scheduled fiber supplement, 82 00:02:56,150 --> 00:02:58,535 adding a scheduled stimulant laxative, 83
00:02:58,535 --> 00:03:00,215 or adding methylnaltrexone? 84 00:03:00,215 --> 00:03:02,270 I agree with stimulant laxative. 85 00:03:02,270 --> 00:03:04,250 We'll talk in a
minute about why I 86
00:03:04,250 --> 00:03:05,600 think that's
87
00:03:05,600 --> 00:03:07,985 a better answer than
methylnaltrexone. 88 00:03:07,985 --> 00:03:11,195 So managing opioid- induced constipation, 89 00:03:11,195 --> 00:03:12,800 Opioid-induced constipation 90 00:03:12,800 --> 00:03:14,345 is almost universal, 91 00:03:14,345 --> 00:03:15,950 with scheduled opioids,
92
00:03:15,950 --> 00:03:18,020 almost everybody gets it. 93
00:03:18,020 --> 00:03:20,705 So you really do need
to anticipate it 94
00:03:20,705 --> 00:03:23,000 and tolerance does not
00:03:23,000 --> 00:03:25,610 develop to opioid-
induced constipation. 96
00:03:25,610 --> 00:03:27,065 You go up on the dose,
97
00:03:27,065 --> 00:03:28,190 the constipation gets
98 00:03:28,190 --> 00:03:29,570 worse, it doesn't get better, 99 00:03:29,570 --> 00:03:31,040 the body doesn't
get used to it, 100
00:03:31,040 --> 00:03:33,320 the bowel does not get
used to it over time. 101
00:03:33,320 --> 00:03:34,580 And for patients who are 102
00:03:34,580 --> 00:03:36,454 on scheduled opioids,
103
00:03:36,454 --> 00:03:37,760 they really ought to be on 104 00:03:37,760 --> 00:03:39,770 a scheduled stimulant laxative. 105 00:03:39,770 --> 00:03:42,380 This is a suggested regiment 106 00:03:42,380 --> 00:03:44,510 that is not the only
107
00:03:44,510 --> 00:03:46,640 but this is
typically what I do. 108
00:03:46,640 --> 00:03:48,875 And I'll point out
a couple of things 109
00:03:48,875 --> 00:03:51,800 about managing opioid-
induced constipation. 110 00:03:51,800 --> 00:03:53,360 First of all, I would actually 111 00:03:53,360 --> 00:03:55,145 cross out docusate,
112 00:03:55,145 --> 00:03:57,680 there's actually several very 113 00:03:57,680 --> 00:04:00,590 good placebo-controlled double-blind studies 114 00:04:00,590 --> 00:04:01,730 that really showed
115 00:04:01,730 --> 00:04:03,020 docusate is no better than 116 00:04:03,020 --> 00:04:05,900 placebo in any patient population, 117 00:04:05,900 --> 00:04:07,400 whether they have
serious illness 118
00:04:07,400 --> 00:04:08,735 or whether they
are healthy, 119
00:04:08,735 --> 00:04:10,865 this drug does not
work very well. 120
00:04:10,865 --> 00:04:13,160 And then I'll point
out that you max 121
00:04:13,160 --> 00:04:15,860 out one drug before
you add another drug. 122
00:04:15,860 --> 00:04:17,060 If you'd go back to what 123
00:04:17,060 --> 00:04:18,230 my patient was taking,
124
00:04:18,230 --> 00:04:20,840 she was taking PRN
125 00:04:20,840 --> 00:04:23,300 docusate, PRN milk of magnesia, 126 00:04:23,300 --> 00:04:25,580 PRN Miralax and
what that amounts 127
00:04:25,580 --> 00:04:28,160 to in a day is
she takes the 128
00:04:28,160 --> 00:04:29,300 docusate, it doesn't work, 129
00:04:29,300 --> 00:04:30,740 so four hours
130
00:04:30,740 --> 00:04:32,660 a dose of milk of mag,
that doesn't work, 131
00:04:32,660 --> 00:04:34,910 so four hours after that she takes Miralax.
132
00:04:34,910 --> 00:04:37,205 And she's essentially
taken one dose, 133
00:04:37,205 --> 00:04:39,875 three drugs a day,
134
00:04:39,875 --> 00:04:41,690 which is very low dose.
135
00:04:41,690 --> 00:04:43,280 So max out one drug
136
00:04:43,280 --> 00:04:45,874 first and then
you start adding 137
00:04:45,874 --> 00:04:48,260 and you get to
methylnaltrexone because 138 00:04:48,260 --> 00:04:49,280 methylnaltrexone 139 00:04:49,280 --> 00:04:50,540 is something that's indicated 140 00:04:50,540 --> 00:04:51,950 if you've maxed out
141
00:04:51,950 --> 00:04:53,495 a good bowel regimen.
142
00:04:53,495 --> 00:04:55,310 Schedule your laxatives, 143
00:04:55,310 --> 00:04:56,810 and then adjust accordingly. 144
00:04:56,810 --> 00:04:58,160 If their stools
are too loose, 145
00:04:58,160 --> 00:05:00,215 back off but schedule them, 146
00:05:00,215 --> 00:05:01,400 don't give them PRN.
147 00:05:01,400 --> 00:05:02,570 How do they know whether 148 00:05:02,570 --> 00:05:03,680 they should take
the milk of 149
00:05:03,680 --> 00:05:06,650 mag or the Miralax
or the docusate? 150
00:05:06,650 --> 00:05:08,420 So fiber isn't really
151 00:05:08,420 --> 00:05:10,760 helpful in opioid- induced constipation. 152 00:05:10,760 --> 00:05:14,270 In the words of one of my esteemed colleagues, 153
00:05:14,270 --> 00:05:17,750 opioids turn your
stool to concrete, 154
00:05:17,750 --> 00:05:20,675 adding fiber just gives
you fibrous concrete. 155
00:05:20,675 --> 00:05:22,040 Not that I'm anti-fiber. 156
00:05:22,040 --> 00:05:23,420 Fiber is lovely, it just 157
00:05:23,420 --> 00:05:24,980 does not work for this.
158 00:05:24,980 --> 00:05:26,255 And consider 159 00:05:26,255 --> 00:05:27,920 a peripherally-acting Mu 160 00:05:27,920 --> 00:05:29,810 opioid receptor antagonist 161 00:05:29,810 --> 00:05:30,950 if you've maxed out a bowel 162 00:05:30,950 --> 00:05:32,300 regimen and you
aren't getting 163
00:05:32,300 --> 00:05:33,710 very far and you've
164
00:05:33,710 --> 00:05:35,315 ruled out a bowel
obstruction. 165
00:05:35,315 --> 00:05:37,399 So what are these
166 00:05:37,399 --> 00:05:40,190 acting Mu opioid receptor antagonists? 167 00:05:40,190 --> 00:05:40,820 Well, we're going to talk 168
00:05:40,820 --> 00:05:42,410 about methylnaltrexone first. 169
00:05:42,410 --> 00:05:44,360 It is the first
one that came out. 170
00:05:44,360 --> 00:05:46,760 It first came out
in a sub-q form. 171
00:05:46,760 --> 00:05:47,900 and what it is, is it's
172 00:05:47,900 --> 00:05:50,480 a mu opioid receptor antagonist 173 00:05:50,480 --> 00:05:52,910 that does not cross the
blood-brain barrier. 174 00:05:52,910 --> 00:05:55,910 So it reverses the effect of opioids on 175 00:05:55,910 --> 00:05:56,990 the mu receptor in 176 00:05:56,990 --> 00:05:58,850 the periphery but not
177
00:05:58,850 --> 00:06:00,305 in the central
nervous system. 178
00:06:00,305 --> 00:06:03,320 So it blocks the opioid
effect on the gut, 179 00:06:03,320 --> 00:06:06,890 inducing laxation without reversing 180 00:06:06,890 --> 00:06:08,300 the pain control within
181
00:06:08,300 --> 00:06:09,860 the central nervous system, 182
00:06:09,860 --> 00:06:14,000 and it is highly
effective. If you have 183
00:06:14,000 --> 00:06:15,200 the right diagnosis and
184
00:06:15,200 --> 00:06:16,565 the patient has
opioid-induced 185
00:06:16,565 --> 00:06:18,710 constipation and you give 186
00:06:18,710 --> 00:06:19,760 this and it doesn't work, 187
00:06:19,760 --> 00:06:20,810 and you give a second dose 188
00:06:20,810 --> 00:06:22,340 the next day and
it doesn't work, 189
00:06:22,340 --> 00:06:23,915 question your diagnosis.
190 00:06:23,915 --> 00:06:25,160 It is that effective 191 00:06:25,160 --> 00:06:27,245 for opioid-induced constipation. 192 00:06:27,245 --> 00:06:28,790 But it ain't cheap -
193
00:06:28,790 --> 00:06:30,530 it's about a $100 a dose 194
00:06:30,530 --> 00:06:32,420 and it's dosed
based on weight. 195
00:06:32,420 --> 00:06:34,280 They do have an oral
methylnaltrexone 196
00:06:34,280 --> 00:06:36,620 now. The FDA
indication for 197
00:06:36,620 --> 00:06:38,570 the oral methylnaltrexone pill is
198
00:06:38,570 --> 00:06:41,300 only for non-cancer
related pain. 199
00:06:41,300 --> 00:06:42,950 Bowel obstruction is still 200 00:06:42,950 --> 00:06:44,840 an absolute contraindication and it 201 00:06:44,840 --> 00:06:46,340
is also highly effective 202 00:06:46,340 --> 00:06:48,500 for opioid-induced constipation. 203 00:06:48,500 --> 00:06:51,500 It is 400, the dose is 450 milligrams 204 00:06:51,500 --> 00:06:54,230 a day and it comes as
a 150 milligram pill. 205
00:06:54,230 --> 00:06:56,720 So that's three
tablets once a day. 206
00:06:56,720 --> 00:06:58,730 And it's about $1500 a
207
00:06:58,730 --> 00:07:00,710 month for a one-
month supply. 208 00:07:00,710 --> 00:07:02,360 So it is very expensive. 209 00:07:02,360 --> 00:07:05,720 Naloxegol also is an oral 210 00:07:05,720 --> 00:07:07,100 peripheral-acting Mu 211 00:07:07,100 --> 00:07:08,720 opioid receptor antagonist. 212 00:07:08,720 --> 00:07:10,325 This is a PEGylated derivative 213
00:07:10,325 --> 00:07:11,630 of naloxone, 214 00:07:11,630 --> 00:07:13,339 so that it acts peripherally 215 00:07:13,339 --> 00:07:15,170 without crossing the
blood-brain barrier. 216 00:07:15,170 --> 00:07:16,970 It is also highly effective for 217 00:07:16,970 --> 00:07:19,130 opioid-induced constipation if 218 00:07:19,130 --> 00:07:20,945 you have the
right diagnosis. 219
00:07:20,945 --> 00:07:23,550 Very rare episodes of
opiate withdrawal occur, 220 00:07:23,550 --> 00:07:25,760 predominantly with methadone patients. 221 00:07:25,760 --> 00:07:27,560 Some GI side effects
222
00:07:27,560 --> 00:07:29,540 early on within the
first few days, 223 00:07:29,540 --> 00:07:32,090 again, primarily in patients on methadone. 224 00:07:32,090 --> 00:07:33,620
The downside of the naloxegol 225 00:07:33,620 --> 00:07:35,630 is that it has 226 00:07:35,630 --> 00:07:37,535 multiple drug interactions 227
00:07:37,535 --> 00:07:38,810 that you really have to
228
00:07:38,810 --> 00:07:39,860 make sure that you're
229
00:07:39,860 --> 00:07:42,290 not interacting
with other drugs. 230
00:07:42,290 --> 00:07:44,585 It comes as a low
dose and a high dose 231
00:07:44,585 --> 00:07:48,110 and it's only about
$330 a month. 232 00:07:48,110 --> 00:07:50,330 Just a chart comparing them 233 00:07:50,330 --> 00:07:51,770 and I would just
point out that for 234 00:07:51,770 --> 00:07:53,540 advanced illness or cancer pain, 235 00:07:53,540 --> 00:07:55,460 the subcutaneous methylnaltrexone
236
00:07:55,460 --> 00:07:56,270 is the only one that's
237
00:07:56,270 --> 00:07:57,830 FDA indicated for
238 00:07:57,830 --> 00:07:59,915 opioid-induced constipation. 239 00:07:59,915 --> 00:08:01,760 I would keep your
eyes and ears 240
00:08:01,760 --> 00:08:03,800 open because I suspect in 241
00:08:03,800 --> 00:08:05,180 the coming months and years 242
00:08:05,180 --> 00:08:06,530 we're going to
hear more and more 243
00:08:06,530 --> 00:08:09,290 about the oral products
and their safety in 244
00:08:09,290 --> 00:08:10,520 use in patients with
245
00:08:10,520 --> 00:08:12,950 cancer or serious illness. 246
00:08:12,950 --> 00:08:14,885 So keep your eyes peeled. 247
00:08:14,885 --> 00:08:16,880 Bowel obstruction is
a contraindication 248
00:08:16,880 --> 00:08:18,185 for all of them.
249
00:08:18,185 --> 00:08:20,060 All of them have only have 250
00:08:20,060 --> 00:08:22,685 safety profiles going
out about a year. 251
00:08:22,685 --> 00:08:24,965 Certainly that data
will trick in... 252
00:08:24,965 --> 00:08:27,620 trickle in over time of
safety beyond a year, 253
00:08:27,620 --> 00:08:29,345 but that's something
to consider, 254
00:08:29,345 --> 00:08:32,600 and then the cost as
noted. And all of them, 255
00:08:32,600 --> 00:08:34,250 if you have a bowel
wall that has 256
00:08:34,250 --> 00:08:36,725 integrity issues such as 257 00:08:36,725 --> 00:08:38,210 a cancer growing through it, 258 00:08:38,210 --> 00:08:39,590 you can run the risk
259
00:08:39,590 --> 00:08:42,380 of perforation in
260 00:08:42,380 --> 00:08:43,430 so that's something to think 261 00:08:43,430 --> 00:08:44,540 about as well; that is
262
00:08:44,540 --> 00:08:47,840 a very rare but
catastrophic complication. 263
00:08:47,840 --> 00:08:49,040 And this is kind of how I 264
00:08:49,040 --> 00:08:50,825 think about using it
265
00:08:50,825 --> 00:08:53,270 in an algorithm where
266
00:08:53,270 --> 00:08:55,100 if they have advanced
illness or cancer, 267
00:08:55,100 --> 00:08:57,080 I'm going straight
to the subcu[taneous]. 268 00:08:57,080 --> 00:08:58,880 If they have non-cancer pain, 269 00:08:58,880 --> 00:09:00,140 my question is, do we have 270 00:09:00,140 --> 00:09:02,180 hepatic failure or drug interactions? 271 00:09:02,180 --> 00:09:03,875 If we do, I'm going
272
00:09:03,875 --> 00:09:05,630 to oral methylnaltrexone. 273
00:09:05,630 --> 00:09:06,740 If we don't have that,
274
00:09:06,740 --> 00:09:08,105 you can use either one.
275 00:09:08,105 --> 00:09:09,410 So my take-home points 276 00:09:09,410 --> 00:09:11,585 for opioid-induced constipation, is that 277 00:09:11,585 --> 00:09:13,940 it is virtually universal in patients 278 00:09:13,940 --> 00:09:15,680 on scheduled opioids, 279 00:09:15,680 --> 00:09:18,395 no tolerance
develops over time, 280 00:09:18,395 --> 00:09:18,980 if you're going to 281 00:09:18,980 --> 00:09:20,720 have someone on scheduled opioids, 282 00:09:20,720 --> 00:09:21,770 you should really have them 283
00:09:21,770 --> 00:09:22,970 on a scheduled stimulant 284
00:09:22,970 --> 00:09:27,065 laxative, fiber is a no-no for these patients,
285 00:09:27,065 --> 00:09:29,270 and consider a peripherally-acting 286 00:09:29,270 --> 00:09:31,160 mu opioid receptor antagonist 287 00:09:31,160 --> 00:09:32,345 if you've maxed out
288
00:09:32,345 --> 00:09:34,400 a bowel regimen and
you've ruled out 289
00:09:34,400 --> 00:09:36,440 bowel obstruction.
And the role of 290
00:09:36,440 --> 00:09:37,835 the oral opioid
291 00:09:37,835 --> 00:09:39,590 antagonist in advanced illnesses 292 00:09:39,590 --> 00:09:40,700 and cancer is probably
293
00:09:40,700 --> 00:09:41,930 evolving and we're probably 294
00:09:41,930 --> 00:09:44,345 going to see more and
more about that. Nausea. 295
00:09:44,345 --> 00:09:46,160 This is a young 18-year-old
296
00:09:46,160 --> 00:09:47,480 woman who really has
297 00:09:47,480 --> 00:09:50,750 horrific systemic lupus erythematosus 298 00:09:50,750 --> 00:09:53,495 and she has a severe
destructive arthritis 299
00:09:53,495 --> 00:09:56,390 related to her Lupus,
and that severe 300
00:09:56,390 --> 00:09:57,740 joint pain really limits 301
00:09:57,740 --> 00:10:00,500 her mobility and
her functionality. 302
00:10:00,500 --> 00:10:02,360 In addition to
that, she has 303 00:10:02,360 --> 00:10:03,950 multi-organ dysfunction due to 304 00:10:03,950 --> 00:10:05,240 her lupus and she
305
00:10:05,240 --> 00:10:06,320 does have a limited life 306
00:10:06,320 --> 00:10:07,580 expectancy because of
307
00:10:07,580 --> 00:10:09,995 the severe progressive
308
00:10:09,995 --> 00:10:12,200 So you elect to start
her on hydromorphone, 309 00:10:12,200 --> 00:10:13,700 two milligrams, PO q 310 00:10:13,700 --> 00:10:17,000 four hours PRN
for her pain, 311
00:10:17,000 --> 00:10:19,580 hoping to improve her
function as she has 312
00:10:19,580 --> 00:10:22,565 failed all other
adjuvant therapies. 313
00:10:22,565 --> 00:10:24,110 And 24 hours later
314
00:10:24,110 --> 00:10:25,640 she tells you
she's miserable 315
00:10:25,640 --> 00:10:27,140 with nausea and
vomiting and 316
00:10:27,140 --> 00:10:28,895 cannot take this
medication. 317 00:10:28,895 --> 00:10:31,220 Alternative etiologies of nausea 318 00:10:31,220 --> 00:10:32,570 have been ruled out.
00:10:32,570 --> 00:10:34,880 What is the next best step 320
00:10:34,880 --> 00:10:37,190 to manage her nausea?
Opiate rotate 321 00:10:37,190 --> 00:10:38,765 her to fentanyl, switch her to 322 00:10:38,765 --> 00:10:40,970 IV hydromorphone, add scheduled 323 00:10:40,970 --> 00:10:42,440 prochlorperazine (which is 324 00:10:42,440 --> 00:10:44,840 Compazine), add PRN ondansetron 325 00:10:44,840 --> 00:10:46,610 (which is Zofran)? Alright. 326
00:10:46,610 --> 00:10:47,690 Well I'm going to try and 327
00:10:47,690 --> 00:10:49,340 convince you that
adding scheduled 328 00:10:49,340 --> 00:10:50,540 prochlorperazine is 329 00:10:50,540 --> 00:10:52,235 actually the right
answer here. 330
00:10:52,235 --> 00:10:55,145 So opioid-induced
331
00:10:55,145 --> 00:10:58,100 It's not as common
as we worry about, 332
00:10:58,100 --> 00:10:59,315 but it's not rare.
333
00:10:59,315 --> 00:11:01,070 Depending on what
study you look at it 334 00:11:01,070 --> 00:11:04,520 somewhere between 15% and 40% of patients. 335 00:11:04,520 --> 00:11:06,440 There are multiple
mechanisms by 336
00:11:06,440 --> 00:11:09,080 which opioids cause nausea. 337
00:11:09,080 --> 00:11:10,370 Obviously gut inertia and 338
00:11:10,370 --> 00:11:12,590 constipation is one
of the big ones. 339
00:11:12,590 --> 00:11:15,799 It can affect the
vestibular function 340
00:11:15,799 --> 00:11:17,270 and give nausea that way. 341
00:11:17,270 --> 00:11:18,440 But by far the most
342
00:11:18,440 --> 00:11:20,000 common way that
343
00:11:20,000 --> 00:11:21,470 nausea is through
344
00:11:21,470 --> 00:11:23,570 the chemo receptor
trigger zone. 345
00:11:23,570 --> 00:11:24,995 Here's the kicker though. 346 00:11:24,995 --> 00:11:27,470 Nausea from opioids, patients 347 00:11:27,470 --> 00:11:29,810 develop tolerance to
it and it goes away 348 00:11:29,810 --> 00:11:31,280 in about 90% of 349 00:11:31,280 --> 00:11:33,410 patients in three to seven days, 350 00:11:33,410 --> 00:11:35,330 if you just wait
long enough. 351
00:11:35,330 --> 00:11:38,330 In almost everybody,
the nausea goes away. 352 00:11:38,330 --> 00:11:40,100 Anti-dopaminergic agents are 353 00:11:40,100 --> 00:11:41,360 first-line for opioid-
354
induced nausea and vomiting 355
00:11:42,770 --> 00:11:45,440 and the reason for
that is for nausea 356
00:11:45,440 --> 00:11:46,700 that is relayed through
357
00:11:46,700 --> 00:11:48,290 the chemo receptor
triggers zone, 358 00:11:48,290 --> 00:11:49,790 that's either a dopaminergic 359 00:11:49,790 --> 00:11:51,635 or a serotonergic phenomenon 360 00:11:51,635 --> 00:11:53,240 and you simply, simply need 361
00:11:53,240 --> 00:11:54,920 to know the piece of trivia 362
00:11:54,920 --> 00:11:57,230 that opioids that
go through there as 363 00:11:57,230 --> 00:11:59,510 a dopaminergic phenomenon more 364 00:11:59,510 --> 00:12:01,370 than a serotonergic phenomenon. 365 00:12:01,370 --> 00:12:02,780 And there's little
366
00:12:02,780 --> 00:12:05,390 support the use of one
opioid over another, 367
00:12:05,390 --> 00:12:07,430 meaning that all
of the opioids 368 00:12:07,430 --> 00:12:09,725 induce nausea at equal rates. 369 00:12:09,725 --> 00:12:13,520 Therefore, if you switch opioids on day one, 370
00:12:13,520 --> 00:12:15,710 all you've done is
reset the clock at 371
00:12:15,710 --> 00:12:17,570 0 and they're likely to get 372
00:12:17,570 --> 00:12:19,910 nausea from that
opioid as well. 373
00:12:19,910 --> 00:12:22,130 So the key here
is try not to 374
00:12:22,130 --> 00:12:25,640 switch the opioids until three to seven days 375
00:12:25,640 --> 00:12:27,230 and this is where I
try to treat through 376
00:12:27,230 --> 00:12:29,375 the nausea for three
377
00:12:29,375 --> 00:12:30,800 If we're seven
days out and we're 378 00:12:30,800 --> 00:12:32,510 still struggling with nausea, 379 00:12:32,510 --> 00:12:33,980 then I switch to a different drug. 380 00:12:33,980 --> 00:12:35,150 There was a study that came 381
00:12:35,150 --> 00:12:36,920 out about a year ago
382
00:12:36,920 --> 00:12:39,140 that showed that
tapentadol had 383 00:12:39,140 --> 00:12:40,580 significantly less GI 384 00:12:40,580 --> 00:12:42,365 side effects than oxycodone. 385 00:12:42,365 --> 00:12:44,360 And that's a first study that's really showed 386
00:12:44,360 --> 00:12:46,370 one opioid to be better
387
00:12:46,370 --> 00:12:47,960 than another and it had
388
00:12:47,960 --> 00:12:49,340 less constipation and
389
00:12:49,340 --> 00:12:51,170 less nausea related to it. 390
00:12:51,170 --> 00:12:52,970 So I have to put a
little asterisk there. 391
00:12:52,970 --> 00:12:53,990 It's a single study.
392
00:12:53,990 --> 00:12:56,105 It's only compared
it to oxycodone, 393
00:12:56,105 --> 00:12:59,060 but it is something to
think about and watch 394
00:12:59,060 --> 00:13:00,530 for if you have
someone who has a 395
00:13:00,530 --> 00:13:02,195 really, really touchy gut. 396
00:13:02,195 --> 00:13:03,620 So my take-home points
397
00:13:03,620 --> 00:13:05,870 for nausea and vomiting, 398
00:13:05,870 --> 00:13:09,095 are address alternative
sources of nausea, 399 00:13:09,095 --> 00:13:11,060 try to avoid opioid rotation 400 00:13:11,060 --> 00:13:12,440 in the first five
to seven days - 401
00:13:12,440 --> 00:13:14,960 try to treat through
for five to seven days, 402 00:13:14,960 --> 00:13:16,730 anti-dopaminergic agents are 403 00:13:16,730 --> 00:13:19,355 first line and I
schedule them – 404
00:13:19,355 --> 00:13:20,630 if through that first
405
00:13:20,630 --> 00:13:22,160 five to seven
days and then I 406
00:13:22,160 --> 00:13:24,845 taper them off, and
consider tapentadol 407
00:13:24,845 --> 00:13:26,270 if you have someone
who has a really, 408
00:13:26,270 --> 00:13:27,290 really touchy gut that
409
00:13:27,290 --> 00:13:29,960 you'd need to use...
someone...use it for in 410 00:13:29,960 --> 00:13:32,239 the right situation. Sedation 411 00:13:32,239 --> 00:13:33,545 related to opioids.
412
00:13:33,545 --> 00:13:34,925 If you are interested in 413
00:13:34,925 --> 00:13:36,395 learning more
about this topic, 414
00:13:36,395 --> 00:13:37,820 Dr. Molly Feely speaks at 415
00:13:37,820 --> 00:13:40,355 the annual Mayo Clinic
opioid conference. 416
00:13:40,355 --> 00:13:42,200 Mayo Clinic offers
hundreds of 417 00:13:42,200 --> 00:13:43,670 continuing medical education 418 00:13:43,670 --> 00:13:45,305 conferences worldwide. 419 00:13:45,305 --> 00:13:48,560 Visit ce.mayo.edu and
420
00:13:48,560 --> 00:13:49,610 register today for
421
00:13:49,610 --> 00:13:52,010 the Mayo Clinic
opioid conference. 422 00:13:52,010 --> 00:13:54,290 So this is one of my favorite patients 423 00:13:54,290 --> 00:13:56,570 that I've ever cared
424 00:13:56,570 --> 00:13:58,550 He's 50 years old and he is in 425 00:13:58,550 --> 00:14:00,620 remission from non-
Hodgkin’s lymphoma. 426
00:14:00,620 --> 00:14:02,960 Unfortunately, he had
pretty bad chemotherapy- 427
00:14:02,960 --> 00:14:05,210 induce peripheral
neuropathy for which he 428
00:14:05,210 --> 00:14:07,550 has been on chronic
opioids because 429
00:14:07,550 --> 00:14:09,965 he has failed trials
of everything else. 430
00:14:09,965 --> 00:14:11,435 And when I mean failed
431
00:14:11,435 --> 00:14:13,460 he got horrible edema from 432
00:14:13,460 --> 00:14:15,530 gabapentin and so I
433
00:14:15,530 --> 00:14:17,195 switched him to pregabalin. 434
00:14:17,195 --> 00:14:20,540 You got horrible edema
from pregabalin that I 435
tried to treat through with Lasix and
436
00:14:22,340 --> 00:14:24,500 compression garments;
that did not work. 437 00:14:24,500 --> 00:14:26,585 So I put them on carbamazepine. 438 00:14:26,585 --> 00:14:28,459 The carbamazepine, I successfully 439 00:14:28,459 --> 00:14:29,810 drove his sodium down to 440
00:14:29,810 --> 00:14:33,050 a 108, personal record
for me at the time. 441 00:14:33,050 --> 00:14:35,060 So I put him on topiramate. 442 00:14:35,060 --> 00:14:36,740 If anybody...if
you've ever seen 443
00:14:36,740 --> 00:14:37,760 the issues with
444
00:14:37,760 --> 00:14:39,110 concen...concentration
445
00:14:39,110 --> 00:14:40,595 and memory with topiramate? 446
00:14:40,595 --> 00:14:43,160 He got that. Couldn't
447 00:14:43,160 --> 00:14:45,080 So I put them on lamotrigine. 448 00:14:45,080 --> 00:14:46,400 I don't know if any
of you have had 449 00:14:46,400 --> 00:14:47,480 the luxury of 450 00:14:47,480 --> 00:14:49,490 inducing the lamotrigine rash in 451 00:14:49,490 --> 00:14:51,290 one of your patients;
I'm here to tell you it 452
00:14:51,290 --> 00:14:54,440 is horrible, horrible rash. 453
00:14:54,440 --> 00:14:56,120 And so in the end
I put them on 454 00:14:56,120 --> 00:14:58,100 tricyclics and we literally had 455 00:14:58,100 --> 00:15:00,065 to shock him out of v tach 456
00:15:00,065 --> 00:15:01,835 from the tricyclics.
457
00:15:01,835 --> 00:15:04,070 So he was on
opiates and he had 458
00:15:04,070 --> 00:15:06,230 failed all of the opiates
459 00:15:06,230 --> 00:15:08,390 including methadone until I had 460 00:15:08,390 --> 00:15:10,700 him on a fentanyl patch. 461 00:15:10,700 --> 00:15:12,380 It was a long-time stable dose. 462 00:15:12,380 --> 00:15:14,105 He had no aberrant behavior. 463 00:15:14,105 --> 00:15:16,250 The issue was that the same 464
00:15:16,250 --> 00:15:18,290 with a fentanyl patch
that he'd had with 465
00:15:18,290 --> 00:15:19,730 all of the other opioids is 466
00:15:19,730 --> 00:15:21,320 that they made
him really sleepy 467
00:15:21,320 --> 00:15:23,180 and it was interfering
with his ability 468
00:15:23,180 --> 00:15:25,190 to do his job at work.
469
00:15:25,190 --> 00:15:27,290 And the only medication
that he was on was 470
a 25 microgram fentanyl 471
00:15:29,000 --> 00:15:30,350 patch every other day.
472
00:15:30,350 --> 00:15:33,140 So what's the next
best step to help with 473
00:15:33,140 --> 00:15:36,620 this guy's somnolence?
Add modafinil 474
00:15:36,620 --> 00:15:38,000 (which is Provigil), tell 475
00:15:38,000 --> 00:15:39,140 him he can't be on opioids 476 00:15:39,140 --> 00:15:40,505 anymore because he doesn't have 477 00:15:40,505 --> 00:15:41,840 cancer-related pain, 478 00:15:41,840 --> 00:15:43,550 tell him he should
quit his job and go on 479 00:15:43,550 --> 00:15:45,995 disability, or start him on an SSRI? 480 00:15:45,995 --> 00:15:48,185 I'd agree with
add modafinil. 481
00:15:48,185 --> 00:15:49,550 He actually had multiple 482
people telling him he should 483
00:15:50,750 --> 00:15:51,860 quit his job and go on
484 00:15:51,860 --> 00:15:53,900 disability because of this issue, 485 00:15:53,900 --> 00:15:56,540 and I just think
that would be 486
00:15:56,540 --> 00:15:59,780 a disaster for this
50, 50-year-old guy. 487 00:15:59,780 --> 00:16:02,165 So sedation-related to opioids, 488 00:16:02,165 --> 00:16:03,770 it's not uncommon, but it's 489
00:16:03,770 --> 00:16:05,060 almost always transient
490
00:16:05,060 --> 00:16:06,080 and it usually goes away 491 00:16:06,080 --> 00:16:07,445 in a couple of days. 492 00:16:07,445 --> 00:16:09,635 If it doesn't go away, 493 00:16:09,635 --> 00:16:11,345 what else is going on?
494
00:16:11,345 --> 00:16:13,355 What else are you missing?
495
00:16:13,355 --> 00:16:15,080 Is there sleep apnea?
496
00:16:15,080 --> 00:16:16,190 What other drug got
497
00:16:16,190 --> 00:16:17,960 added? Nine times
out of ten 498 00:16:17,960 --> 00:16:19,940 it's a benzodiazepine or a muscle 499 00:16:19,940 --> 00:16:22,580 relaxer, but what else
500
00:16:22,580 --> 00:16:24,890 is going on that's
driving the sedation if 501
00:16:24,890 --> 00:16:27,470 it doesn't go away in
two to three days. 502
00:16:27,470 --> 00:16:29,780 And really, step three
503
00:16:29,780 --> 00:16:31,580 is really what
else is going on? 504
00:16:31,580 --> 00:16:34,385 Is this person hypogonadal from the opioids?
505
00:16:34,385 --> 00:16:35,780 Are there alternative drugs 506
00:16:35,780 --> 00:16:37,130 other than the opioids?
507
00:16:37,130 --> 00:16:38,180 Can you switch them to
508 00:16:38,180 --> 00:16:40,130 a non-opioid medication? 509 00:16:40,130 --> 00:16:42,500 I think we definitively gave 510 00:16:42,500 --> 00:16:44,990 that our very best shot
with this patient. 511 00:16:44,990 --> 00:16:48,485 Opioid...Is opioid rotation an option? 512 00:16:48,485 --> 00:16:50,210 What else can we do?
513
00:16:50,210 --> 00:16:52,040 Because the last thing is 514 00:16:52,040 --> 00:16:53,930 to add a stimulant medication. 515 00:16:53,930 --> 00:16:56,615 And as both a family doc 516
00:16:56,615 --> 00:16:57,830 and a general internist, 517
00:16:57,830 --> 00:16:59,330 I hate treating
the side effect 518
00:16:59,330 --> 00:17:00,830 of one drug with
519
00:17:00,830 --> 00:17:02,720 but this is a case in
520 00:17:02,720 --> 00:17:04,640 a rare situation where I would 521 00:17:04,640 --> 00:17:05,780 consider doing it with
522
00:17:05,780 --> 00:17:07,010 a stimulant medication.
523
00:17:07,010 --> 00:17:08,480 The two stimulants
out there that 524
00:17:08,480 --> 00:17:09,890 we use are methylphenidate, 525
00:17:09,890 --> 00:17:12,530 (or Ritalin) or modafinil (or Provigil).
526
00:17:12,530 --> 00:17:13,550 They really have very
527 00:17:13,550 --> 00:17:15,769 similar side effect profiles 528 00:17:15,769 --> 00:17:18,245 with some anxiety,
some tremulousness, 529 00:17:18,245 --> 00:17:20,000 some cardiac dysrhythmia that 530 00:17:20,000 --> 00:17:22,460 is usually atrial in
531
00:17:22,460 --> 00:17:27,230 nature, usually but not
always, insomnia and 532 00:17:27,230 --> 00:17:29,300 anorexia is listed by side effect. 533 00:17:29,300 --> 00:17:30,530 I will tell you
I've never seen 534
00:17:30,530 --> 00:17:31,700 that in an adult yet.
535
00:17:31,700 --> 00:17:33,560 I've never seen an
adult who had had 536
00:17:33,560 --> 00:17:35,615 significant problems
with that yet. 537
00:17:35,615 --> 00:17:38,630 The tips that I would
say is don't give 538
00:17:38,630 --> 00:17:39,830 the second dose after
539
00:17:39,830 --> 00:17:41,570 2:00 PM or they're
not going to sleep. 540
00:17:41,570 --> 00:17:45,650 So I usually dose it at
eight and noon or eight and two, 541
00:17:45,650 --> 00:17:46,970 but I won't go...but I try 542
00:17:46,970 --> 00:17:48,965 not to give it
after two o'clock. 543
00:17:48,965 --> 00:17:50,600 Methylphenidate is twice a day, 544
00:17:50,600 --> 00:17:52,490 I usually use modafinil once a day;
545
00:17:52,490 --> 00:17:54,275 it's a little bit
longer-acting. 546 00:17:54,275 --> 00:17:55,610 So my sedation take-home 547 00:17:55,610 --> 00:17:57,455 points are:
it’s usually transient, 548
00:17:57,455 --> 00:17:59,000 try to wait a couple days, 549
00:17:59,000 --> 00:18:00,920 it almost always gets
better and go away, 550
00:18:00,920 --> 00:18:02,090 if it doesn't
get better and 551
00:18:02,090 --> 00:18:03,380 go away, I really,
552
00:18:03,380 --> 00:18:04,970 really look hard to try and 553
00:18:04,970 --> 00:18:06,710 figure out what
554
00:18:06,710 --> 00:18:08,150 And I would use
stimulants as 555
00:18:08,150 --> 00:18:09,650 an...as a last resort
556
00:18:09,650 --> 00:18:12,665 and only in the
right patient. Pruritus. 557
00:18:12,665 --> 00:18:14,180 So this is a 24-year-old 558
00:18:14,180 --> 00:18:15,410 young man who
is admitted to 559
00:18:15,410 --> 00:18:16,640 the hospital with a tib/fib 560
00:18:16,640 --> 00:18:18,320 fracture one night,
561
00:18:18,320 --> 00:18:20,180 planning to go to the
operating room the next 562
00:18:20,180 --> 00:18:22,835 morning to have a rod
put in his leg. 563 00:18:22,835 --> 00:18:24,500 Upon admission to the hospital, 564 00:18:24,500 --> 00:18:26,600 he had reported allergies to morphine, 565 00:18:26,600 --> 00:18:28,925 codeine, oxycodone,
and hydrocodone. 566
00:18:28,925 --> 00:18:31,250 Now why 24-year-old has
567
00:18:31,250 --> 00:18:32,750 had exposure to morphine, 568 00:18:32,750 --> 00:18:34,610 codeine, oxycodone, 569 00:18:34,610 --> 00:18:36,320 hydrocodone would probably have 570 00:18:36,320 --> 00:18:38,180 been a good thing
for me to ask. 571
00:18:38,180 --> 00:18:39,980 At the time, I didn't
572
00:18:39,980 --> 00:18:42,050 he complaints of
pain and his pain 573 00:18:42,050 --> 00:18:45,965 is uncontrolled by non-opioid regiments. 574 00:18:45,965 --> 00:18:47,600 So I ordered PO 575 00:18:47,600 --> 00:18:50,360 hydromorphone for his
pain and he almost 576
00:18:50,360 --> 00:18:52,160 immediately
started itching, his 577
exam showed no rash. 578
00:18:53,675 --> 00:18:55,535 So how would you
manage his itching? 579 00:18:55,535 --> 00:18:57,425 Switch him to IV hydromorphone, 580 00:18:57,425 --> 00:19:00,020 add PRN diphenhydramine, schedule 581 00:19:00,020 --> 00:19:02,120 at a dean, switch him to nalbuphine. 582 00:19:02,120 --> 00:19:03,230 I'm going to try
and convince you 583
00:19:03,230 --> 00:19:04,580 that actually switching
584
00:19:04,580 --> 00:19:05,630 him to nalbuphine is
585
00:19:05,630 --> 00:19:07,235 probably the best
answer here. 586 00:19:07,235 --> 00:19:09,650 So opioid-induced pruritus. 587 00:19:09,650 --> 00:19:11,900 So first of all, pruritus, is not an allergy.
588
00:19:11,900 --> 00:19:13,970 You can have an
589
00:19:13,970 --> 00:19:16,550 but a true opioid allergy usually presents as 590 00:19:16,550 --> 00:19:17,690 hives or anaphylaxis 591 00:19:17,690 --> 00:19:20,375 and it's very impressive, 592
00:19:20,375 --> 00:19:22,340 and not very subtle. The pruritus 593
00:19:22,340 --> 00:19:24,035 and the itching
that people get 594
00:19:24,035 --> 00:19:25,790 from opioids that is more 595 00:19:25,790 --> 00:19:28,145 common is actually not an allergy. 596 00:19:28,145 --> 00:19:33,110 It is common and it is
far more common with 597
00:19:33,110 --> 00:19:35,510 intrathecal or
axial opioids than 598 00:19:35,510 --> 00:19:38,060 it is with systemic opioids. 599 00:19:38,060 --> 00:19:41,300 And it is not a histamine- related phenomenon.
600
00:19:41,300 --> 00:19:43,040 It is true that opioids
601
00:19:43,040 --> 00:19:44,840 cause mast cell release, 602
00:19:44,840 --> 00:19:47,960 but it is not mast cell
release or histamine- 603
00:19:47,960 --> 00:19:50,255 related that causes the itching 604
00:19:50,255 --> 00:19:51,875 that people get
with opioids. 605
00:19:51,875 --> 00:19:53,720 So please, quit snowing
606
00:19:53,720 --> 00:19:55,700 these people with
Benadryl. 607
00:19:55,700 --> 00:19:57,140 They do sleep and they quit 608 00:19:57,140 --> 00:19:59,360 complaining because they’re schnockered, 609 00:19:59,360 --> 00:20:01,100 but they wake up itching. 610
00:20:01,100 --> 00:20:03,440 Unfortunately, there
is very little data 611
00:20:03,440 --> 00:20:05,000 on how to manage
612
00:20:05,000 --> 00:20:07,235 the itching outside of
613 00:20:07,235 --> 00:20:09,485 the intrathecal administration, 614 00:20:09,485 --> 00:20:10,940 which makes it challenging. 615
00:20:10,940 --> 00:20:12,560 And management is largely 616
00:20:12,560 --> 00:20:14,255 based on expert opinion. 617
00:20:14,255 --> 00:20:16,670 So these are my tips
618 00:20:16,670 --> 00:20:19,475 for opioid- induced pruritus. 619 00:20:19,475 --> 00:20:20,870 So for reasons we don't
620 00:20:20,870 --> 00:20:23,720 understand, hydromorphone, fentanyl, oxymorphone, 621 00:20:23,720 --> 00:20:25,940 and tramadol seem to
622
00:20:25,940 --> 00:20:28,160 have less itching
associated with them. 623 00:20:28,160 --> 00:20:29,900 So that is always my first step. 624 00:20:29,900 --> 00:20:31,100 If they're on oxycodone 625
00:20:31,100 --> 00:20:33,080 or hydrocodone or morphine, 626
00:20:33,080 --> 00:20:35,779 and I have the opportunity 627
00:20:35,779 --> 00:20:37,055 to opiate rotate them,
628
00:20:37,055 --> 00:20:39,110 these drugs
might cause less 629
00:20:39,110 --> 00:20:40,730 itching and some patients 630
00:20:40,730 --> 00:20:42,410 will tolerate
them much better. 631 00:20:42,410 --> 00:20:43,715 Oral or IV makes 632 00:20:43,715 --> 00:20:45,740 no difference. Naloxone 633 00:20:45,740 --> 00:20:47,330 is indeed really, 634 00:20:47,330 --> 00:20:49,010 really effective for getting 635 00:20:49,010 --> 00:20:50,975 rid of the opioid-
induced etching. 636 00:20:50,975 --> 00:20:52,190 The problem is it 637 00:20:52,190 --> 00:20:54,440
also reverses their pain control
638
00:20:54,440 --> 00:20:56,420 and so that doesn't
really help you much in 639
00:20:56,420 --> 00:20:59,675 the practical management of these patients. 640 00:20:59,675 --> 00:21:02,000 Partial opioid agonists such as 641 00:21:02,000 --> 00:21:04,580 nalbuphine or butorphanol, 642 00:21:04,580 --> 00:21:06,680 butorphanol is Stadol, nalbuphine is Nubain, 643 00:21:06,680 --> 00:21:09,485 seem to really
reduce itching a lot. 644
00:21:09,485 --> 00:21:11,090 These studies have
mostly been done in 645 00:21:11,090 --> 00:21:13,265 patients on intrathecal opioids, 646 00:21:13,265 --> 00:21:15,170 so their pain is being managed by 647 00:21:15,170 --> 00:21:17,210 their intrathecal
pump and they're 648
00:21:17,210 --> 00:21:18,650 given small doses of
649
00:21:18,650 --> 00:21:21,335 these opioids solely
to manage the itching, 650
00:21:21,335 --> 00:21:22,970 not to manage the pain.
651
00:21:22,970 --> 00:21:25,220 How you manage this
in someone like 652
00:21:25,220 --> 00:21:27,380 my patient who was having 653
00:21:27,380 --> 00:21:30,110 it based on systemic,
and how you use 654
00:21:30,110 --> 00:21:31,250 these medicines to treat 655
00:21:31,250 --> 00:21:34,115 both pain and itching
is less clear. 656
00:21:34,115 --> 00:21:35,840 I will tell you
with my guy, 657
00:21:35,840 --> 00:21:37,880 I went with Nubain
because I was somewhat 658
00:21:37,880 --> 00:21:39,200 familiar with it and using 659
00:21:39,200 --> 00:21:40,310 it in pregnant women.
00:21:40,310 --> 00:21:41,540 It was a very interesting 661
00:21:41,540 --> 00:21:42,830 20-minute conversation
662
00:21:42,830 --> 00:21:44,390 with the nighttime
pharmacists, 663
00:21:44,390 --> 00:21:45,470 trying to convince him
664
00:21:45,470 --> 00:21:47,000 that my 24-year-old man, 665
00:21:47,000 --> 00:21:48,860 I was indeed ordering
Nubain for 666
00:21:48,860 --> 00:21:50,510 my 24-year-old man and
667 00:21:50,510 --> 00:21:52,010 no, he was not pregnant. 668 00:21:52,010 --> 00:21:53,450 But I eventually got it up, 669
00:21:53,450 --> 00:21:55,310 we used it for his
pain and it worked 670
00:21:55,310 --> 00:21:56,390 beautifully for both his 671
00:21:56,390 --> 00:21:57,755 pain and his itching.
672
00:21:57,755 --> 00:22:01,429 If this is a mu
receptor phenomenon, 673 00:22:01,429 --> 00:22:03,065 if the itching is actually caused 674 00:22:03,065 --> 00:22:05,270 by a mu receptor phenomenon. 675 00:22:05,270 --> 00:22:06,860 How about these
peripherally- 676
00:22:06,860 --> 00:22:09,560 acting Mu, opioid
receptor antagonists? 677
00:22:09,560 --> 00:22:10,310 While in fact there are
678
00:22:10,310 --> 00:22:11,360 a couple of
studies out there 679
00:22:11,360 --> 00:22:14,150 now looking at managing
680 00:22:14,150 --> 00:22:15,740 itching with methylnaltrexone. 681 00:22:15,740 --> 00:22:17,015 And disappointingly, 682 00:22:17,015 --> 00:22:18,980 it hasn't worked in any of them. 683 00:22:18,980 --> 00:22:20,450 There's a reasonably good 684
double-blind
placebo-controlled trial 685
00:22:22,370 --> 00:22:24,200 of 72 patients that had no, 686
00:22:24,200 --> 00:22:25,805 no benefit over placebo. 687
00:22:25,805 --> 00:22:28,400 That probably suggests
that this is more 688
00:22:28,400 --> 00:22:29,720 a central phenomenon than 689 00:22:29,720 --> 00:22:31,250 a peripheral phenomenon 690 00:22:31,250 --> 00:22:32,300 and that makes sense
691
00:22:32,300 --> 00:22:33,440 based on that we see the 692 00:22:33,440 --> 00:22:35,180 itching more common in intra- 693 00:22:35,180 --> 00:22:37,115 thecal and axial opioids. 694
00:22:37,115 --> 00:22:38,660 And the other thing
is, there might be 695
00:22:38,660 --> 00:22:39,950 a serotonin component to 696
00:22:39,950 --> 00:22:42,470 this because the serotonin
697
00:22:42,470 --> 00:22:45,425 blockers seem to
help the itching. 698
00:22:45,425 --> 00:22:47,930 There's not good
data for this, 699
00:22:47,930 --> 00:22:50,510 but using ondansetron,
700 00:22:50,510 --> 00:22:52,730 which is a serotonergic blocker or, 701 00:22:52,730 --> 00:22:54,080 mirtazapine, 702 00:22:54,080 --> 00:22:55,850 in some studies have shown 703 00:22:55,850 --> 00:22:58,340 some benefit in managing itching. 704 00:22:58,340 --> 00:23:00,815 I had a cancer
patient on high doses 705
00:23:00,815 --> 00:23:04,295 of oxymorphone who
had terrible itching
706
00:23:04,295 --> 00:23:06,650 and we put him
on scheduled 707
00:23:06,650 --> 00:23:07,940 ondansetron four times a 708
day and didn't
eliminate the itching, 709
00:23:09,620 --> 00:23:11,660 but it made it...
decreased it enough to 710
00:23:11,660 --> 00:23:13,820 make it tolerable
for him to continue 711
00:23:13,820 --> 00:23:15,290 therapy. So my take-home 712
00:23:15,290 --> 00:23:16,790 points - it's not histamine, 713
00:23:16,790 --> 00:23:18,260 please stop the Benadryl. 714
00:23:18,260 --> 00:23:20,585 Consider a
partial agonist drug, 715 00:23:20,585 --> 00:23:22,580 if that's an option, and possibly 716 00:23:22,580 --> 00:23:24,410 consider ondansetron or 717 00:23:24,410 --> 00:23:27,185 mirtazapine if...if...as a, 718 00:23:27,185 --> 00:23:28,475 as a management tool. 719 00:23:28,475 --> 00:23:29,960 So Dr. Feely we have a few 720
specific questions 721
00:23:30,680 --> 00:23:31,550 about side effects for you. 722
00:23:31,550 --> 00:23:33,380 So what do you think about 723
00:23:33,380 --> 00:23:34,880 the person who's
on scheduled 724 00:23:34,880 --> 00:23:36,080 chronic narcotics, 725 00:23:36,080 --> 00:23:38,405 who denies they ever
have any constipation? 726
00:23:38,405 --> 00:23:40,115 Are they full of it?
I had... 727
00:23:40,115 --> 00:23:41,510 I had one patient who had 728 00:23:41,510 --> 00:23:43,070 chronic diarrhea who, getting 729 00:23:43,070 --> 00:23:44,660 on chronic opioids for her 730
00:23:44,660 --> 00:23:46,280 calciphylaxis, was
the best thing that 731
00:23:46,280 --> 00:23:48,080 ever happened to her. And I 732
00:23:48,080 --> 00:23:49,940 had her on nothing
for laxatives because 733
00:23:49,940 --> 00:23:52,235 the opioid solved her
chronic diarrhea. 734 00:23:52,235 --> 00:23:53,930 So it can happen, 735 00:23:53,930 --> 00:23:55,985 but it is few
and far between. 736
00:23:55,985 --> 00:23:56,780 And then how would you
737 00:23:56,780 --> 00:23:57,920 handle a patient who develops 738 00:23:57,920 --> 00:24:00,200 extrapyramidal symptoms on the prochlorperazine 739 00:24:00,200 --> 00:24:01,250 that you're using to
740
00:24:01,250 --> 00:24:02,840 treat their nausea?
741
00:24:02,840 --> 00:24:04,100 I would put them on something 742 00:24:04,100 --> 00:24:05,810 that's not a dopaminergic blocker. 743 00:24:05,810 --> 00:24:06,710 You'd...you'd have to go 744 00:24:06,710 --> 00:24:07,670 to something else because
745
00:24:07,670 --> 00:24:10,100 that's a side effect
of all dopaminergic 746 00:24:10,100 --> 00:24:12,020 antagonist drugs. 747 00:24:12,020 --> 00:24:13,370 And so you're going
to have to go 748 00:24:13,370 --> 00:24:16,775 to ondansetron or something else. 749 00:24:16,775 --> 00:24:18,050 We've had a couple questions 750 00:24:18,050 --> 00:24:18,830 throughout the morning about 751 00:24:18,830 --> 00:24:21,005 hypogonadism as a side effect. 752 00:24:21,005 --> 00:24:23,210 And is that resolved simply by 753 00:24:23,210 --> 00:24:24,430 removing the opioid or
754
00:24:24,430 --> 00:24:25,340 is there ever a role for, 755
00:24:25,340 --> 00:24:27,290 for example,
testosterone treatment? 756
00:24:27,290 --> 00:24:29,030 It is actually resolved
757
00:24:29,030 --> 00:24:30,710 with getting them
off the opioids. 758
00:24:30,710 --> 00:24:32,630 The hypogonadism goes away, 759
00:24:32,630 --> 00:24:34,850 all of the woman who got 760
00:24:34,850 --> 00:24:37,385 pregnant as her
dose came down. 761 00:24:37,385 --> 00:24:39,650 So the ideal situation would be 762 00:24:39,650 --> 00:24:41,870 to get them off the
opioids if they, 763
00:24:41,870 --> 00:24:44,000 if their diseases
such that getting 764
00:24:44,000 --> 00:24:46,520 them off the opioids
is not an option, 765
00:24:46,520 --> 00:24:48,755 treating them with
testosterone is effective. 766
00:24:48,755 --> 00:24:50,330 What's the rationale
for changing 767
00:24:50,330 --> 00:24:52,280 q2 two days?
768
00:24:52,280 --> 00:24:54,050 And then it would
769 00:24:54,050 --> 00:24:56,465 ketamine be an alternative to fentanyl, 770 00:24:56,465 --> 00:24:57,170 when you're thinking
771
00:24:57,170 --> 00:24:58,340 about peri-operative use? 772
00:24:58,340 --> 00:25:00,335 For perioperative pain control, 773
00:25:00,335 --> 00:25:03,710 fentanyl patches are
work every third day 774 00:25:03,710 --> 00:25:07,370 for about 98 to 99% of people. 775 00:25:07,370 --> 00:25:10,130 And then there are some
people who are simply 776 00:25:10,130 --> 00:25:12,890 faster metabolizers and they 777 00:25:12,890 --> 00:25:14,630 will see the dose
778
00:25:14,630 --> 00:25:16,070 will wear off on
that third day. 779
00:25:16,070 --> 00:25:17,840 And they'll come in
and say, I'm great, 780
00:25:17,840 --> 00:25:20,150 except that third day
is horrible. 781
00:25:20,150 --> 00:25:21,980 And so in those patients 782
00:25:21,980 --> 00:25:23,390 going to an,
every other day, 783
00:25:23,390 --> 00:25:26,705 fentanyl at the same
dose is very effective. 784
00:25:26,705 --> 00:25:28,430 I've seen that
predominantly in 785
00:25:28,430 --> 00:25:30,230 people who are profoundly 786
00:25:30,230 --> 00:25:32,240 cachectic and my hospice 787
00:25:32,240 --> 00:25:34,144 patients at the
very end of life,
788
00:25:34,144 --> 00:25:35,660 but the other
place where I've seen 789
00:25:35,660 --> 00:25:37,250 it is in real young people. 790
00:25:37,250 --> 00:25:38,270 Do you think that there's 791
an opioid that causes 792
00:25:39,170 --> 00:25:41,810 less delirium and our
elderly patients or 793
00:25:41,810 --> 00:25:44,585 one that you would
choose over another? No, 794
00:25:44,585 --> 00:25:46,190 and it's not tramadol.
795
00:25:46,190 --> 00:25:48,530 They all have equal,
equal delirium. 796
00:25:48,530 --> 00:25:50,375 We've been talking
about management of 797
00:25:50,375 --> 00:25:52,730 opioid side effects
with Dr. Molly Feely, 798 00:25:52,730 --> 00:25:54,020 consultant in the division of 799 00:25:54,020 --> 00:25:55,460 General Internal Medicine 800
00:25:55,460 --> 00:25:57,035 at Mayo Clinic, Rochester. 801
00:25:57,035 --> 00:25:59,525 Remember, if you enjoyed Mayo Clinic Talks,
802
00:25:59,525 --> 00:26:01,805 please subscribe and
803 00:26:01,805 --> 00:26:03,740 Healthcare professionals looking to claim 804 00:26:03,740 --> 00:26:05,780 CME credit for
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00:26:05,780 --> 00:26:08,405 The Opioid Edition, go to 806
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